2,6-Di-tert-butyl-4-(2′-thenoyl)phenol(R-830): A novel nonsteroidal anti-inflammatory agent with antioxidant properties

Moore, G. G. I.; Swingle, Karl F.

doi:10.1007/bf01965078

Cited by 40 publications

(18 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…y-Oryzanol is reported to exhibit similar antioxidant activity [ 13]. A new series of hydrogen transfer, chain-break ing antioxidants with high lipophilicity, have recently been synthesized [14,15], This group of compounds protect well against several types of radicals [16] and decrease MDA production when phenolic liposomes are oxidized [17], Figure 1 illustrates the chemical structure of the two drugs found to be most effective in the present study. These compounds share a functional hydroxyl group on the phenol ring which is the hydro gen donor for their action.…”

Section: Discussionmentioning

confidence: 99%

Preventive Effect of Antioxidants on Lipid Peroxidation in the Retina

Hiramitsu

Armstrong

1991

Ophthalmic Res

View full text Add to dashboard Cite

Lipid peroxidation was induced with porcine retinal homogenates using ferric iron or UV light. A number of lipid and aqueous-soluble antioxidants were tested and their protective effects measured after 60 min of exposure. The iron system produced up to 5 times more lipid hydroperoxides as quantified by the fluorescense thiobarbituric acid (TBA) assay. Of the three substituted dialkyl phenols evaluated, the most efficient was compound S-17224 which was able to afford > 90% protection at 10^––4 M concentration in the iron-induced system. At 10^––5 M, inhibition was 78% and at 10^––6 M 33%. By comparison, 10^––4 M γ-oryzanol inhibited the reaction by 61 % and α-tocopherol by only 14%. The combination of 10^––6 M S-17224 and 10^––4 M γ-oryzanol potentiated the effect by another 23%. In the light-catalyzed system. S-17224 and α-tocopherol were more efficient (71%). The model system described here is simple and can be employed to study additional antioxidants as well as in the retinotoxic evaluation of ophthalmic drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Preventive Effect of Antioxidants on Lipid Peroxidation in the Retina

Hiramitsu

Armstrong

1991

Ophthalmic Res

View full text Add to dashboard Cite

show abstract

“…Biological results obtained with these drugs can be summarized as follow R-830 (19) was demonstrated to be a potent inhibitor of guinea pig lung lipoxygenases and bovine seminal vesicle cyclooxygenase [152]. R-830 also inhibited PGE 2 production by stimulated rat synovial cells with an IC 50 of 0.003 µM and significantly inhibited LTB 4 production by human neutrophils stimulated with the calcium ionophore A 23187 [152]. Furthermore, compound (19) was an effective anti-inflammatory drug in several animal models of acute and chronic inflammation such as the carrageenan-induced paw edema and adjuvant arthritis in rats.…”

Section: Di-tert-butylphenol Class and Derivativesmentioning

confidence: 98%

New Trends in Dual 5-LOX / COX Inhibition

Leval¹,

Julémont²,

Delarge³

et al. 2002

CMC

109

View full text Add to dashboard Cite

Dual inhibitors are drugs able to block both the COX and the 5-LOX metabolic pathways. The interest of developing such compounds is supported by a large number of pharmacological studies. Compared to COX or LOX pathways single inhibitors, dual inhibitors present at least two major advantages. First, dual inhibitors, by acting on the two major arachidonic acid metabolic pathways, possess a wide range of anti-inflammatory activity. Secondly, dual inhibitors appear to be almost exempt from gastric toxicity, which is the most troublesome side effect of COX inhibitors. The mechanism of their gastric-sparing properties is not completely understood, although it has been demonstrated that leukotrienes significantly contribute to the gastric epithelial injury. Finally, both COX and LOX derivatives (prostanoids and leukotrienes, respectively) are involved in other diseases than inflammation such as cancer proliferation where the use of dual inhibitors could be an interesting approach.

show abstract

“…Thus, combined HPLC and RIA provides extra confidence in the identity of the analyte being measured. The relative merits of extensive sample purification prior to the use of certain analytical techniques has recently been reviewed [1][2][3][4][5][6][7][8][9][10][11][12][13].…”

Section: Ltb4 Extraction and Analysismentioning

confidence: 99%

“…Compounds of diverse structural series have been synthesized as putative inhibitors of 5-LO, including derivatives of phenol [1] and catechol [2]. These compounds have potential therapeutic use as antiinflammatory agents by virtue of their ability to block the production of sulphidopeptide leukotrienes LTC4, LTD4, and LTE4 [3,4], which are implicated in the development of asthma, and LTB4, which is a potent chemotactic agent thought to contribute to the lung damage of cystic fibrosis [-5, 6].…”

Section: Introductionmentioning

confidence: 99%

Lipoxygenase inhibitory activity of U-66,858 and its deacetylated metabolite U-68,244 in human whole blood

1994

View full text Add to dashboard Cite

The inhibitory effects of the semi-quinone U-66,858 and its metabolite U-68,244 on the ionophore-induced formation of leukotriene B4 (LTB4) were examined in human whole blood (WB). Preincubation of U-66,858 and U-68,244 for 1 min prior to challenge of blood with calcium ionophore A23187 resulted in IC50 values of 1080 +/- 644 and 820 +/- 442 nmol/L, respectively (NS). After 60 min preincubation, values were 250 +/- 85 and 270 +/- 79 nmol/L (NS). The activity of the lipoxygenase inhibitor AA-861 in this system was similar to that of U-66,858, while vitamin K and the sulphate conjugate of U-66,858 showed significant inhibition of LTB4 release only at micromolar concentrations. U-66,858 exhibited significant inhibition of thromboxane A2 release (p < 0.02) in a comparative study with the known cyclooxygenase (CO) inhibitor flurbiprofen. The metabolism of U-66,858 in contact with WB at 37 degrees C was monitored for 70 min using [14C]-labelled drug and reverse-phase HPLC, the majority of recovered radioactivity no longer in the form of U-66,858 being accounted for by U-68,244 and polar conjugates of U-66,858. Thus, U-66,858 is a potent inhibitor of LTB4 production in human whole blood and undergoes deacetylation to an initial metabolite with similar pharmacological potency. However, other metabolites of U-66,858 such as the sulphate conjugate, are relatively weak inhibitors of 5-lipoxygenase (5-LO) under similar conditions.

show abstract

2,6-Di-tert-butyl-4-(2′-thenoyl)phenol(R-830): A novel nonsteroidal anti-inflammatory agent with antioxidant properties

Cited by 40 publications

References 39 publications

Preventive Effect of Antioxidants on Lipid Peroxidation in the Retina

Preventive Effect of Antioxidants on Lipid Peroxidation in the Retina

New Trends in Dual 5-LOX / COX Inhibition

Lipoxygenase inhibitory activity of U-66,858 and its deacetylated metabolite U-68,244 in human whole blood

Contact Info

Product

Resources

About